The present invention provides for a method and apparatus for inserting and using dermal interstitial sensors in, for example, an analyte monitoring system.
The dermis, the second layer of the skin, is usually described as a densely compacted layer of fibroconnective tissue through which course small branches of arteries, veins and lymphatic vessels, as well as nerves. Recent data obtained by correlation of histologic findings with in vivo microscopy reveal that this appearance of densely compacted fibroconnective tissue is artefactual; the living dermis is a cavernous interstitial sinus supported and defined by an extensive lattice of thick collagen bundles lined on one side by a CD34+ cell without endothelial ultrastrucure: perhaps a modified endothelial cell, a fibroblast, and/or mesenchymal stem cell. The interstitial fluid flowing in this space in living tissue is derived from serum and may be considered pre-lymph. Molecules in the serum reach the interstitial fluid within minutes of change, as demonstrated by intravascular infusion of fluorescein whereby, within minutes, in vivo microscopy reveals fluorescence of the dermal interstitial sinus.
This lymph, imprecisely termed “interstitial fluid”, contains biomolecules, such as proteins, glycoproteins, sugars, lipids, etc, as they are found in the blood. Indwelling sensors that can detect such molecules are known, in particular glucose sensors that are inserted into the skin. However, inventors and users of these devices are imprecise in their identification of the “interstitial fluid” that is being monitored and of the precise location and anatomy of device insertion. These devices often decline in signal integrity over time and also have skin irritative effects that require regular replacement, perhaps due to the invasion of deeper tissues generating tissue reactions. The lack of understanding of the anatomy of the dermal lymphatic sinus has led to such imprecisions which this present invention alleviates.
This present invention describes a method of placement of such a sensor so that it lies entirely within the dermal lymphatic sinus or reticular dermis, providing consistent and maximal exposure to lymph. The device would be positioned by first inserting a trocar at a shallow angle into the dermal lymphatic sinus or reticular dermis, removal of the obturator component leaving the hollow cannula. Lymph draining from the cannula confirms correct placement and then the sensor device is slipped through the cannula and cannula is removed, leaving the device in place, fully within the dermal lymphatic sinus or reticular dermis. This device may be connected to:
An external device for registering and transmission of data from the sensor to nearby or distant monitors;
An internal device sufficiently small to also lay contained within the dermal lymphatic sinus;
An internal device surgically embedded in soft tissues beneath the dermis, i.e., in the subcutis.
The device to which the sensor communicates can receive signals through direct physical connections or wireless digital signaling, such as, but not limited to, Bluetooth.
The sensor can measure glucose or other analytes, such as ions, proteins and glycoproteins, lipids, other sugars, ingested nutrients or drugs/toxins or their metabolites.
The sensor can be coated with biologic or synthetic molecules (including, but not limited to chitosan, hyaluronic acid, Teflon®, glycosaminoglycans such as Heparin, Heparin sulfate, chondroitin sulfate etc. that are antifibrotic and/or anti-inflammatory around the sensor leading to consistent signaling over time greater than is achieved through current, imprecisely placed sensors.
Uses for the device would include continuous monitoring of blood sugar in patients with type 1 or type 2 diabetes mellitus, electrolyte imbalances in individuals in exposed environmental conditions such as soldiers and extreme sports participants, uric acid levels in patients with gout, etc.
According to the American Diabetes Association in 2012, 29.1 million Americans, or 9.3% of the population, had diabetes.
Approximately 1.25 million American children and adults have type 1 diabetes.
Undiagnosed: Of the 29.1 million, 21.0 million were diagnosed, and 8.1 million were undiagnosed.
Prevalence in Seniors: The percentage of Americans age 65 and older remains high, at 25.9%, or 11.8 million seniors (diagnosed and undiagnosed).
New Cases: 1.4 million Americans are diagnosed with diabetes every year.
Prediabetes: In 2012, 86 million Americans age 20 and older had prediabetes; this is up from 79 million in 2010.
Deaths: Diabetes remains the 7th leading cause of death in the United States in 2010, with 69,071 death certificates listing it as the underlying cause of death, and a total of 234,051 death certificates listing diabetes as an underlying or contributing cause of death.
Diabetes in Youth
About 208,000 Americans under age 20 are estimated to have diagnosed diabetes, approximately 0.25% of that population.
Diabetes may be underreported as a cause of death. Studies have found that only about 35% to 40% of people with diabetes who died had diabetes listed anywhere on the death certificate and about 10% to 15% had it listed as the underlying cause of death.
The key to good health for a diabetic is to monitor their blood glucose levels regularly to be able to maintain a healthy lifestyle. Blood sticks have long been the method for daily monitoring but they are painful and burdensome which leads to a lack of compliance among those who are at risk.
A finger-prick blood glucose check gives you only one number in time. It's hard to know: Is your blood glucose rising, falling, or staying steady? A continuous glucose monitor (CGM), however, records hundreds of readings a day.
A CGM consists of three parts: a small under-the-skin sensor that measures glucose levels in what is known as interstitial fluid; a transmitter that attaches to the sensor and transfers data; and a receiver that displays glucose information and stores data. The sensor measures glucose every five minutes or so.
According to Diabetes Self-Management; although studies find that the sensor readings usually are close to fingerstick numbers, there can be significant differences (up to 15%). It takes glucose around 5-10 minutes to move from blood into tissue fluid, or back, so the CGM measures lag behind what's really happening in your blood if things are changing rapidly.
The CGM doesn't replace fingersticks. You still have to check your blood glucose level 2 to 4 times a day to keep the CGM calibrated. Calibration is an ongoing job with CGMS. They also say you should not make “treatment decisions” (like taking extra insulin) based on a CGMS reading without taking a conventional blood glucose reading first.
Acceptance of CGM in the diabetic community has been slow because of a number of reasons. They are not reliable due to variabilities in placement of the sensor, the fat level of the individual and the high costs which are not always covered by insurance.
The present invention provides for multiple means for a variety of health monitoring that are a reliable means of placement of CGM and similar type interstitial sensors and the use of a digital device that can alternatively read a test strip in a more rapid low cost means of monitoring glucose among other constituents.
All references cited herein are incorporated herein by reference in their entireties.